Pembrolizumab followed by irreversible electroporation of a liver metastasis in pancreatic cancer patients

Preclinical studies suggest that irreversible electroporation (IRE) increases the effect of immune checkpoint inhibition in pancreatic cancer (PC). Patients with PC received PD-1 inhibitor pembrolizumab and, on day 10, percutaneous IRE of a liver metastasis. Blood samples were analyzed for immune cell subsets and inflammation related proteins. mRNA expression profiling was done in sequential biopsies. Treatment was safe, but the trial was terminated early. The response rate in eight patients was 0% and tumor growth was exponential. A drop in circulating plasmacytoid dendritic cells and a rise in several cytokines and proteins, especially PD-1, after immunotherapy was observed. In liver metastases, immune stimulatory genes were upregulated and immune suppressive genes were downregulated after pembrolizumab, while markers of effector T cells were unchanged. Treatment was safe but showed no efficacy in PC. Immunotherapy induced an immune permissive tumor microenvironment but with no increase in effector cells.